Metabolic kinetics of isoniazid in rabbits

The metabolic kinetics of isoniazid (INH) was studied with 6 rabbits by i.v. administration of 0.109 mole kg^-1 of the following compounds: INH, acetylisoniazid (AcINH), isonicotinic acid (INA), sodium pyruvate isonicotinoyl hydrazone (INH-K Na) and sodium α-ketoglutarate isonicotinoyl hydrazone (INH-kNA). By the principle of area analysis, the formation fraction was 0.302 ± 0.073 for INH-P and 0.105 ± 0.014 for AcINH formed from INH. A inverse linear relationship (r = -0.9892, p <0.01) between the above two metabolites formed from INH was observed, which showed the formation clearance of AcINH decreased as that of INH-P increased in the same rabbit. The formation fraction of INA hydrolyzed from INH was 0.067 ± 0.008. After AcINH had been administered, 0.231 ± 0.035 of the dose was hydrolyzed to INA. Therefore, INA might be formed either directly from INH hydrolysis or from AcINH hydrolysis. However, the former was the predominant pathway. The smallest amount of metabolite formed from INH was INH-K. After INH-K administration, 0.373 ± 0.065 of the dose was metabolized to INH-P.